C1GALT1C1

Summary

Gene Symbol: C1GALT1C1
Description: C1GALT1 specific chaperone 1
Alias: C1GALT2, C38H2-L1, COSMC, HSPC067, MST143, TNPS, C1GALT1-specific chaperone 1, C38H2-like protein 1, beta 1,3-galactosyltransferase 2, core 1 beta1,3-galactosyltransferase 2, core 1 beta3-Gal-T2, core 1 beta3-galactosyltransferase-specific molecular chaperone
Species: human
Products:     C1GALT1C1

Top Publications

  1. Ju T, Cummings R. Protein glycosylation: chaperone mutation in Tn syndrome. Nature. 2005;437:1252 pubmed
    ..Here we show that Tn syndrome is associated with a somatic mutation in Cosmc, a gene on the X chromosome that encodes a molecular 'chaperone' that is required for the proper folding and hence ..
  2. Ju T, Lanneau G, Gautam T, Wang Y, Xia B, Stowell S, et al. Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer Res. 2008;68:1636-46 pubmed publisher
    ..common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase...
  3. Mi R, Song L, Wang Y, Ding X, Zeng J, Lehoux S, et al. Epigenetic silencing of the chaperone Cosmc in human leukocytes expressing tn antigen. J Biol Chem. 2012;287:41523-33 pubmed publisher
    b>Cosmc is the specific molecular chaperone in the endoplasmic reticulum for T-synthase, a Golgi ?3-galactosyltransferase that generates the core 1 O-glycan, Gal?1-3GalNAc?-Ser/Thr, in glycoproteins...
  4. Ju T, Cummings R. A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc Natl Acad Sci U S A. 2002;99:16613-8 pubmed
    ..We report here that C1beta3Gal-T activity requires expression of a molecular chaperone designated Cosmc (core 1 beta3-Gal-T-specific molecular chaperone)...
  5. Kudo T, Iwai T, Kubota T, Iwasaki H, Takayma Y, Hiruma T, et al. 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. J Biol Chem. 2002;277:47724-31 pubmed
    ..These results indicated that C1Gal-T2 is the second candidate for core 1 synthase that plays an important role in synthesizing O-glycans in digestive organs. ..
  6. Ju T, Aryal R, Stowell C, Cummings R. Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc. J Cell Biol. 2008;182:531-42 pubmed publisher
    ..Formation of active T-synthase, which resides in the Golgi apparatus, requires a unique molecular chaperone, Cosmc, encoded on Xq24...
  7. Malycha F, Eggermann T, Hristov M, Schena F, Mertens P, Zerres K, et al. No evidence for a role of cosmc-chaperone mutations in European IgA nephropathy patients. Nephrol Dial Transplant. 2009;24:321-4 pubmed publisher
    ..The galactosyltransferase core-1 beta3-galactosyltransferase-1 (C1GALT1) and its chaperone cosmc are specifically required for O-galactosylation of the IgA1 hinge region...
  8. Aryal R, Ju T, Cummings R. Tight complex formation between Cosmc chaperone and its specific client non-native T-synthase leads to enzyme activity and client-driven dissociation. J Biol Chem. 2012;287:15317-29 pubmed publisher
    The interaction of the endoplasmic reticulum molecular chaperone Cosmc with its specific client T-synthase (Core 1 ?1-3-galactosyltransferase) is required for folding of the enzyme and eventual movement of the T-synthase to the Golgi, ..
  9. Qin W, Zhong X, Fan J, Liu X, Li Z, Ma X. [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. 2011;42:762-5 pubmed
    To investigate the effect of methylation modification on the mRNA expression of Cosmc gene in peripheral B lymphocytes from IgA nephropathy (IgAN). Biopsy identified 22 cases of IgAN patients and 20 cases of normal control were included...

More Information

Publications54

  1. Li G, Zhang H, Lv J, Shen Y, Wang H. Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney Int. 2007;71:448-53 pubmed
    ..study was performed to investigate the association between single-nucleotide polymorphisms (SNPs) of C1GALT1 and C1GALT1C1 genes and the susceptibility to IgAN...
  2. Sahasrabudhe N, Lenos K, van der Horst J, Rodriguez E, van Vliet S. Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3. Biol Chem. 2018;399:649-659 pubmed publisher
    ..involved in the synthesis or elongation of Tn antigen, N-acetylgalactosamine-transferases (GALNTs) and C1GalT1/COSMC, respectively. Both the activity and expression of C1GalT1 and COSMC were unrelated to the BRAF mutational status...
  3. Soni K, Thomas D, Caffrey T, Mehla K, Lei F, O Connell K, et al. Polymeric Nanogel-based Treatment Regimen for Enhanced Efficacy and Sequential Administration of Synergistic Drug Combination in Pancreatic Cancer. J Pharmacol Exp Ther. 2019;: pubmed publisher
    ..More than 80% of the PDAC aberrantly expresses Sialyl Tn (STn) antigen due to the loss of function of COSMC, a specific chaperone for the activity of core 1 β3-galactosyltransferase or C1GalT...
  4. Liu Y, Liu B, Li Y, Li Y, Du J, Deng S, et al. Autophagy is involved in the differentiation of epicardial progenitor cells into vascular smooth muscle cells in mice. Exp Cell Res. 2019;375:60-71 pubmed publisher
    ..early transient differentiation of EPCs, enhanced migration ability and weakened systolic function, but overall, CoSMC development is still inhibited...
  5. Wolters Eisfeld G, Mercanoglu B, Hofmann B, Wolpers T, Schnabel C, Harder S, et al. Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice. Exp Mol Med. 2018;50:133 pubmed publisher
    b>Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase. Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins...
  6. Sun X, Ju T, Cummings R. Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal cancers. BMC Cancer. 2018;18:827 pubmed publisher
    ..Studies in several Tn-expressing cancer cell lines and pancreatic tumors have identified loss of Cosmc expression caused by either mutations or promoter hypermethylation...
  7. Chang D, Gao F, Slavney A, Ma L, Waldman Y, Sams A, et al. Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases. PLoS ONE. 2014;9:e113684 pubmed publisher
    ..a transcription factor that regulates T-cell development and function, with vitiligo; and (4) we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs...
  8. Shao J, Peng Y, He L, Liu H, Chen X, Peng X. Capsaicin induces high expression of BAFF and aberrantly glycosylated IgA1 of tonsillar mononuclear cells in IgA nephropathy patients. Hum Immunol. 2014;75:1034-9 pubmed publisher
    ..were higher in IgAN patients than that in non-IgAN patients, meanwhile, the gene expression of C1GALT1 and Cosmc and IgA1 O-glycosylation level were significantly lower...
  9. Coelho R, Marcos Silva L, Mendes N, Pereira D, Brito C, Jacob F, et al. Mucins and Truncated O-Glycans Unveil Phenotypic Discrepancies between Serous Ovarian Cancer Cell Lines and Primary Tumours. Int J Mol Sci. 2018;19: pubmed publisher
    ..explored the role of truncating the O-glycosylation capacity in OVCAR3 cells through knockout of the COSMC chaperone, using in vitro and in vivo assays...
  10. Gioia L, Siddique A, Head S, Salomon D, Su A. A genome-wide survey of mutations in the Jurkat cell line. BMC Genomics. 2018;19:334 pubmed publisher
    ..INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1)...
  11. Beatson R, Maurstad G, Picco G, Arulappu A, Coleman J, Wandell H, et al. 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. 2015;10:e0125994 pubmed publisher
    ..The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells...
  12. Campos D, Freitas D, Gomes J, Magalhães A, Steentoft C, Gomes C, et al. Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery. Mol Cell Proteomics. 2015;14:1616-29 pubmed publisher
    ..However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, ..
  13. Stolfa G, Mondal N, Zhu Y, Yu X, Buffone A, Neelamegham S. Using CRISPR-Cas9 to quantify the contributions of O-glycans, N-glycans and Glycosphingolipids to human leukocyte-endothelium adhesion. Sci Rep. 2016;6:30392 pubmed publisher
    ..Here, O-glycan biosynthesis was truncated by knocking-out Core 1 β3Gal-T Specific Molecular Chaperone (COSMC), N-glycans by targeting the β1,2 GlcNAc-transferase (MGAT1) and GSLs by deleting UDP-glucose ceramide ..
  14. Yang L, Zhang X, Peng W, Wei M, Qin W. MicroRNA-155-induced T lymphocyte subgroup drifting in IgA nephropathy. Int Urol Nephrol. 2017;49:353-361 pubmed publisher
    ..GATA-3, SOCS-1, and Fxop3), cytokines (IFN-?, IL-5, IL-10, and IL-17), serum IgA1 glycosylation level, and Cosmc expression were examined using flow cytometry, qPCR, and ELISA...
  15. Jacobs J, Lin L, Goudarzi M, Ruegger P, McGovern D, Fornace A, et al. Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency. Gut Microbes. 2017;8:1-16 pubmed publisher
    ..Polymorphisms near C1galt1 (rs10486157) and its molecular chaperone, Cosmc (rs4825729), were associated with altered composition of the colonic mucosal microbiota, supporting the relevance ..
  16. Kudelka M, Hinrichs B, Darby T, Moreno C, Nishio H, Cutler C, et al. Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk. Proc Natl Acad Sci U S A. 2016;113:14787-14792 pubmed publisher
    ..Core 1 β3GalT-specific molecular chaperone (Cosmc), which encodes an X-linked chaperone important for glycocalyx formation, was recently identified as an IBD risk ..
  17. Ju T, Wang Y, Aryal R, Lehoux S, Ding X, Kudelka M, et al. Tn and sialyl-Tn antigens, aberrant O-glycomics as human disease markers. Proteomics Clin Appl. 2013;7:618-31 pubmed publisher
    ..STn antigens is compromised T-synthase activity, resulting from alteration of the X-linked gene that encodes for Cosmc, a molecular chaperone specifically required for the correct folding of T-synthase to form active enzyme...
  18. Munkley J. The Role of Sialyl-Tn in Cancer. Int J Mol Sci. 2016;17:275 pubmed publisher
    ..to the expression of the sialytransferase ST6GalNAc1, and also to mutations in and loss of heterozygosity of the COSMC gene...
  19. Xie Y, He L, Chen X, Peng X, Ye M, Zhao Y, et al. Potential diagnostic biomarkers for IgA nephropathy: a comparative study pre- and post-tonsillectomy. Int Urol Nephrol. 2016;48:1855-1861 pubmed
    The proteins BAFF, ST6GALNAC2, C1GALT1, and COSMC in peripheral blood mononuclear cells (PBMCs) and plasma levels of IgA1 and galactose-deficient IgA1 (Gd-IgA1) are potential biomarkers for IgAN nephropathy...
  20. Aryal R, Ju T, Cummings R. Identification of a novel protein binding motif within the T-synthase for the molecular chaperone Cosmc. J Biol Chem. 2014;289:11630-41 pubmed publisher
    ..that the core 1 ?3-galactosyltransferase (T-synthase) is a specific client of the endoplasmic reticulum chaperone Cosmc, whose function is required for T-synthase folding, activity, and consequent synthesis of normal O-glycans in all ..
  21. Wakui H, Fuseya S, Suzuki R, Shimbo M, Okada R, Hamada M, et al. Incomplete clearance of apoptotic cells by core 1-derived O-glycan-deficient resident peritoneal macrophages. Biochem Biophys Res Commun. 2018;495:2017-2023 pubmed publisher
    The core 1 β1,3-galactosyltransferase-specific molecular chaperon (Cosmc) is essential for the synthesis of the core 1 structure of mucin-type O-glycans...
  22. Hanes M, Moremen K, Cummings R. Biochemical characterization of functional domains of the chaperone Cosmc. PLoS ONE. 2017;12:e0180242 pubmed publisher
    b>Cosmc is an endoplasmic reticulum chaperone necessary for normal protein O-GalNAc glycosylation through regulation of T-synthase, its single client...
  23. Yu X, Du Z, Sun X, Shi C, Zhang H, Hu T. Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29. Int J Clin Exp Pathol. 2015;8:2590-602 pubmed
    The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase...
  24. Narimatsu Y, Kubota T, Furukawa S, Shimojima M, Iwasaki H, Tozawa Y, et al. Co-translational function of Cosmc, core 1 synthase specific molecular chaperone, revealed by a cell-free translation system. FEBS Lett. 2011;585:1276-80 pubmed publisher
    ..Core 1 synthase specific molecular chaperone (Cosmc), a molecular chaperone specific for C1GalT, is essential for the expression of functional C1GalT in mammalian ..
  25. Mascarenhas J, Korokhov N, Burger L, Kassim A, Tuter J, Miller D, et al. Genetic engineering of CHO cells for viral resistance to minute virus of mice. Biotechnol Bioeng. 2017;114:576-588 pubmed publisher
    ..transporter, solute carrier family 35A1 (Slc35a1), the core 1-?-1,3-galactosyltransferase-1 specific chaperone (Cosmc), and mannosyl (?-1,3-)-glycoprotein ?-1,2-N-acetylglucosaminyltransferase (Mgat1) as well as members of the ..
  26. Xiao J, Wang M, Xiong D, Wang Y, Li Q, Zhou J, et al. TGF-?1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 ?1, 3-galactosyltransferase and Cosmc. Mol Med Rep. 2017;15:969-974 pubmed publisher
    ..The mRNA levels of core1 ?1, 3-galactosyltransferase (C1GalT1) and its molecular chaperone, Cosmc, were analyzed, as was the subsequent O-glycosylation of IgA1, in a human B?cell line stimulated with TGF??1...
  27. Lee J, Chen C, Chen Y, Huang M, Huang J, Hung J, et al. COSMC is overexpressed in proliferating infantile hemangioma and enhances endothelial cell growth via VEGFR2. PLoS ONE. 2013;8:e56211 pubmed publisher
    Infantile hemangiomas are localized lesions comprised primarily of aberrant endothelial cells. COSMC plays a crucial role in blood vessel formation and is characterized as a molecular chaperone of T-synthase which catalyzes the synthesis ..
  28. Xie Q, Mo X, Liu S, Zhu M, Tao Y, Zhang X, et al. [Association of Cosmc gene mutation with susceptibility to Henoch-Schönlein purpura in children]. Zhongguo Dang Dai Er Ke Za Zhi. 2016;18:625-9 pubmed
    To investigate the presence of Cosmc gene mutation in children with Henoch-Schönlein purpura (HSP) and the association between Cosmc gene mutation and the susceptibility to HSP...
  29. Hu S, Bao H, Xu X, Zhou X, Qin W, Zeng C, et al. Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy. FEBS Lett. 2015;589:4019-25 pubmed publisher
    ..Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN...
  30. Hofmann B, Schlüter L, Lange P, Mercanoglu B, Ewald F, Fölster A, et al. COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. Mol Cancer. 2015;14:109 pubmed publisher
    ..Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties...
  31. Ho C, Lin C, Liaw Y, Chiang H, Chin Y, Huang R, et al. The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. Oncotarget. 2016;7:61930-61944 pubmed publisher
    ..Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands ..
  32. Sun Q, Zhang J, Zhou N, Liu X, Shen Y. DNA methylation in Cosmc promoter region and aberrantly glycosylated IgA1 associated with pediatric IgA nephropathy. PLoS ONE. 2015;10:e0112305 pubmed publisher
    ..The expression of the specific molecular chaperone of core1ß1, 3galactosyl transferase (Cosmc) is known to be reduced in IgAN...
  33. Aryal R, Ju T, Cummings R. The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. J Biol Chem. 2010;285:2456-62 pubmed publisher
    ..Here we describe the novel ability of an endoplasmic reticulum-localized molecular chaperone termed Cosmc to specifically interact with partly denatured T-synthase in vitro to cause partial restoration of activity...
  34. Li G, Nie G, Zhang H, LV J, Shen Y, Wang H. Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?. BMC Med Genet. 2009;10:101 pubmed publisher
    ..Cosmc, encoded by C1GALT1C1 gene, was indispensable to beta1,3 galactosylation of IgA1...
  35. Fu J, Wei B, Wen T, Johansson M, Liu X, Bradford E, et al. Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice. J Clin Invest. 2011;121:1657-66 pubmed publisher
    ..Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia...
  36. Crew V, Singleton B, Green C, Parsons S, Daniels G, Anstee D. New mutations in C1GALT1C1 in individuals with Tn positive phenotype. Br J Haematol. 2008;142:657-67 pubmed publisher
    Tn polyagglutination results from inactivating mutations in C1GALT1C1, an X-borne gene encoding a core 1 beta3-galactosyltransferase-specific molecular chaperone (cosmc) required for the functioning of T-synthase (beta 1,3-..
  37. Shi C, Xu X, Yu X, Du Z, Luan X, Liu D, et al. CD3/CD28 dynabeads induce expression of tn antigen in human t cells accompanied by hypermethylation of the cosmc promoter. Mol Immunol. 2017;90:98-105 pubmed publisher
    ..product, Tn antigen, arises from somatic mutations in core1?3-galactosyltransferase-specific molecular chaperone (Cosmc), which is required for the formation of active core1?3-galactosyltransferase (T-synthase)...
  38. Huang J, Che M, Lin N, Hung J, Huang Y, Lin W, et al. The molecular chaperone Cosmc enhances malignant behaviors of colon cancer cells via activation of Akt and ERK. Mol Carcinog. 2014;53 Suppl 1:E62-71 pubmed publisher
    ..b>Cosmc is a molecular chaperone required for the formation of an active T-synthase, which catalyzes the synthesis of T ..
  39. Yoo N, Kim M, Lee S. Absence of COSMC gene mutations in breast and colorectal carcinomas. APMIS. 2008;116:154-5 pubmed publisher
  40. Xie L, Qin W, Fan J, Huang J, Xie X, Li Z. The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. Clin Invest Med. 2010;33:E5-13 pubmed
    ..This study attempted to determine the role of C1GALT1C1 in aberrant IgA1 O-glycosylation induced by lipopolysaccharide (LPS) and identify potential therapeutic targets ..
  41. Narimatsu Y, Ikehara Y, Iwasaki H, Nonomura C, Sato T, Nakanishi H, et al. Immunocytochemical analysis for intracellular dynamics of C1GalT associated with molecular chaperone, Cosmc. Biochem Biophys Res Commun. 2008;366:199-205 pubmed
    ..core structure, is synthesized by cooperation of core 1 synthase (C1GalT) and its specific molecular chaperone, Cosmc. The chaperone function of Cosmc has been well investigated biochemically...
  42. Kiryluk K, Li Y, Moldoveanu Z, Suzuki H, Reily C, Hou P, et al. GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway. PLoS Genet. 2017;13:e1006609 pubmed publisher
    ..2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8)...
  43. Zeng J, Mi R, Wang Y, Li Y, Lin L, Yao B, et al. Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation. J Biol Chem. 2015;290:19018-33 pubmed publisher
    The T-synthase (core 1 β3-galactosyltransferase) and its molecular chaperone Cosmc regulate the biosynthesis of mucin type O-glycans on glycoproteins, and evidence suggests that both T-synthase and Cosmc are transcriptionally ..
  44. Yang M, Li F, Xie X, Wang S, Fan J. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells. Biochem Biophys Res Commun. 2014;444:276-81 pubmed publisher
    ..which at least partly attributed to the downregulation of ?1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN ..
  45. Sun Q, Ju T, Cummings R. The transmembrane domain of the molecular chaperone Cosmc directs its localization to the endoplasmic reticulum. J Biol Chem. 2011;286:11529-42 pubmed publisher
    ..We recently discovered a novel ER molecular chaperone termed Cosmc, which is essential for folding and normal activity of the Golgi enzyme T-synthase...