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evolution
in contrast to cellular homologues, this virus has evolved to alternatively express two proteins from gene Bo17
evolution
the enzyme belongs to the GT14 family
evolution
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the viral 17 gene encodes a functional homologue of the cellular Corebeta1,6GnT typeM(C2GnT-M), which was acquired from a recent ancestor of the African buffalo. Bo17 splicing is conserved among BoHV-4 strains but not in its cellular counterparts
evolution
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in contrast to cellular homologues, this virus has evolved to alternatively express two proteins from gene Bo17
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malfunction
C2GnT2 deficiency, impair of mucosal barrier, increase of susceptibility to colitis, reduced immunoglobulin abundance, loss of all core 4 O-glycan biosynthetic activity
malfunction
C2GnT3 deficiency, reduced thyroxine levels in circulation
malfunction
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higher presence of the enzyme in higher stages of testicular germ cell tumors, promotes aggressive behavior of cancer cells
malfunction
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in C2GlcNAc-TI deficient mice, decreased monocyte interactions, inhibition of monocyte recruitment, formation of small, macrophage-poor and collagen-rich atherosclerotic lesions
malfunction
a Bo17 knockout strain does not display any growth deficit in vitro. But sole expression of either of the two Bo17-encoded proteins could influence BoHV-4 growth
malfunction
aberrant GCNT3 expression is associated with increased mucin production, aggressive tumorigenesis, and reduced patient survival, and CRISPR-mediated knockout of GCNT3 in pancreatic cancer cells reduces proliferation and spheroid formation. Inhibitor talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro
malfunction
GCNT1-overexpressing cells produce a significantly larger amount of growth factors when cocultured with prostate stromal cells compared with GCNT1-knocked down cells and form larger tumors
malfunction
in mouse pancreatic cancer tumors, GCNT3 103fold upregulation is correlated with increased expression of mucins by 5-87fold. Inhibitor talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro. CRISPR GCNT3-KO leads to reduced cell viability and spheroid formation
malfunction
loss of C2GnT-M leads to development of colitis and colon cancer. Knockdown of KRT1 by siRNA does not affect Golgi morphology but leaves C2GnT-M outside of the Golgi, resulting in the formation of sialyl-T antigen
malfunction
Gcnt1-/-Th1 cells lacking C2-GlcNAcT-I expression show impaired P-lig expression similar to Fut4+7-/-Th1 cells. In contrast to impaired P-lig expression,Gcnt1-/-and Fut4 +7-/- maintain their inflammatory competence as assessed by IFNgamma expression. Functional relevance of Gcnt1 deficiency in CD4+T cells in vivo. In line with a lack of Gcnt1 transcription, naive T cells exhibit a closed histone configuration with lowH3K4me2 and prominent H3K27me3 marks. The active H3K4me2 mark in this region increases in a time-dependent manner during Th1 differentiation
malfunction
GCNT3 overexpression reduces 5-fluorouracil resistance in colorectal cancer (CRC) cells. GCNT3 overexpression reduces proliferation, invasion and changes metabolic capacities of CRC cells. The enzyme's overexpression in epithelial ovarian cancer (EOC) patients is associated with better clinical outcome and response to initial therapy
malfunction
miR-BART1-5p directly targets GCNT3. In addition, miR-BART1-5p mimics transfection is observed to reduce cell proliferation and migration, while miR-BART1-5p inhibitor increases cell proliferation and migration following transfection. In conclusion, both miR-BART1-5p and knockdown of GCNT3 inhibit cell proliferation and migration
malfunction
silencing and functional inhibition of GCNT3 greatly suppresses migration and invasion of melanoma cells, resulting in the loss of S100A8/A9 responsiveness. siRNA-mediated GCNT3 suppression and talniflumate-mediated GCNT3 suppression significantly attenuate the basal ability of in vitro migration of WM-266-4 cells
malfunction
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the Bo17 knockout strain does not display any growth deficit in vitro
malfunction
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in mouse pancreatic cancer tumors, GCNT3 103fold upregulation is correlated with increased expression of mucins by 5-87fold. Inhibitor talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro. CRISPR GCNT3-KO leads to reduced cell viability and spheroid formation
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malfunction
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a Bo17 knockout strain does not display any growth deficit in vitro. But sole expression of either of the two Bo17-encoded proteins could influence BoHV-4 growth
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metabolism
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the enzyme is required for the generation of P-selectin
metabolism
O-glycan biosynthesis pathways and proposed O-glycan structures of selected glycosyltransferases, overview. Core 1 dominates the O-glycan repertoire. Core 1 can be further elongated by extended C1 beta3GnT3 enzyme, EC 2.4.1.146, to form extended core 1 structure, or be modified by C2 beta6GnT1 enzyme to form core 2 O-glycans. Three core 2 enzymes, C2 beta6GnT1, 2, and 3, are responsible for biosynthesis of core 2 O-glycans. C2 beta6GnT1 and 3 are almost exclusively responsible for biosynthesis of the core 2 branch, while C2 beta6GnT2 shows a significant core 4 and I-branching activity. Regulation of O-glycan biosynthesis, overview
metabolism
the enzyme is involved in the biosynthetic pathways for core2 O-glycans, overview. The core1 structure is converted to branched core2 structure (Core2) by GCNT1, GCNT3, and GCNT4
metabolism
as all fucosyltransferases 8 (FUT8), GnT-III, GnT-IV, and GnT-V use GlcNAc terminated bi-antennary glycan as acceptor substrate, the interplay among these enzymes determines the forms of glycans, e.g. the bisecting modification by GnT-III makes the glycan no longer a substrate for FUT8 and GnT-V
metabolism
integrated transcriptomic and proteomic analyses reveal that GCNT3 is linked to cellular cycle, mitosis and proliferation, response to drugs and metabolism pathways. The vascular epithelial growth factor A (VEGFA) arises as an attractive partner of GCNT3 functions in cell invasion and resistance
physiological function
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induces tumor-specific T-cell responses
physiological function
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leukocyte recruitment to the arterial wall
physiological function
Bovine herpesvirus 4 modulates its beta-1,6-N-acetylglucosaminyltransferase activity through alternative splicing. The enzyme is a homologue of the cellular core 2 protein beta-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M), which is a key player for the synthesis of complex O-glycans
physiological function
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C2GnT1 synthesizes the core 2 branching structure by catalysing the transfer of GlcNAc from UDP-GlcNAc with a beta1,6-linkage to GalNAc of the core 1 chain. On this core 2 branch, several tumour-associated carbohydrate structures, such as sLex and sLea, are synthesized. The enzyme may be associated with the biological aggressiveness of tumour cells, relationship between the expression of C2GnT1 and clinicopathological parameters of patients with endometrial carcinoma, overview
physiological function
core 2 beta-1, 6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans. GCNT1 expression is correlated with D'Amico's recurrence risk classification. GCNT1-negative tumors are associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. GCNT1 expression status is an independent risk factor for PSA recurrence after radical prostatectomy
physiological function
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enzyme GCNT1 expression in prostate cancer specimens from radical prostatectomy correlates with prostate cancer aggressiveness
physiological function
mucin-type isozyme core 2 N-acetylglucosaminyltransferase 2/M synthesizes all three beta6GlcNAc branch structures found in secreted mucins
physiological function
the isozyme shows tumour suppressor properties, together with a role of mucin production in chemotherapy sensitivity in pancreatic cancer
physiological function
the mucin-synthesizing core 2 beta-1,6 N-acetylglucosaminyltransferase (GCNT3/C2GNT) plays a significant role in mucin biosynthesis
physiological function
the mucin-synthesizing core 2 beta-1,6 N-acetylglucosaminyltransferase (GCNT3/C2GNT) plays a significant role in mucin biosynthesis. Correlation between GCNT3 expression and patient survival in human pancreatic cancer
physiological function
beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) is a glycosyltransferase that transfers GlcNAc to N-acetylgalactosamine (GalNAc) of the core 1 acceptor structure to form the core 2 branch in the beta-1,6 linkage. In addition to the formation of the core 2 structure, GCNT3 also functions to form the core 4 structure. GCNT3 increases MCAM stability, which enhances S100A8/A9-mediated cancer motility. Among the novel S100A8/A9 receptors, GCNT3 favorably glycosylates the MCAM receptor, extending its half-life and leading to further elevation of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 plays a pivotal role in the maintenance of MCAM protein at a high level, resulting in the acquisition of strong responsiveness to S100A8/A9 that is linked to increased cellular migration and invasion. GCNT3 expression is positively correlated to MCAM expression in patients with high-grade melanomas. GCNT3 is an upstream regulator of MCAM protein. GCNT3 plays a key role in S100A8/A9-mediated cancer motility. GCNT3 controls MCAM stability by its catalytic activity-mediated glycosyl modification that correlates with a greater ability for cancer cell motility and invasion in response to extracellular S100A8/A9
physiological function
core 2 beta1,6-N-acetylglucosaminyltransferase-I (C2GlcNAcT-I) is crucial for inflammatory homing of Th1 cells to the skin in vivo, analysis of molecular regulation of the enzyme encoded by gene Gcnt1 in CD4+T helper cells, overview. C2-GlcNAcT-I, encoded by Gcnt1, is essential for generation of P-lig and recruitment of Th1 cells into a skin-DTH reaction. Gcnt1 transcription and subsequent P-lig induction in Th1 cells is governed by binding of STAT4 and T-bet to a distal enhancer and further regulated by epigenetic marks such as H3K27me3. T-cells cultured in vitro under Th1 conditions, i.e. supplemented with IL-12, IFN gamma, and anti-IL-4, but not under Th2 (IL-4, anti-IL-12, anti-IFN gamma) or Th0 (anti-12, anti-IFNgamma and anti-IL-4) conditions, express P-lig, which corresponds to differential Gcnt1 but not Fut7 mRNA expression. STAT4 controls Gcnt1 expression in Th1 cells, several several conserved and non-conserved predicted STAT4 binding sites are determined. Functional importance of STAT4 for P-lig induction and specifically on the enhancer as a transactivating factor. Prolonged T-bet binding to the Gcnt1 enhancer
physiological function
O-glycan synthase glucosamine (N-acetyl) transferase 3 (GCNT3) is a mucin-type responsible for catalyzing core 2 and core 4 O-glycans and forming O-linked glycosylation in protein biosynthesis. Abnormal expression of GCNT3 promotes the progression of several human cancers. GCNT3 expression in Epstein-Barr virus (EBV)-associated gastric cancer cells and tissues is lower than in EBV-negative gastric cancer cells and tissues, and high expression is significantly associated with advanced tumor-lymph node metastasis. EBV may regulate GCNT3 by affecting the NF-kappaB signaling pathway. Patients with EBV-associated gastric cancer (EBVaGC) have a good survival rate. EBV potentially regulates GCNT3 by affecting the NF-kappaB signaling pathway
physiological function
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the Bo17 gene is nonessential for virus replication, despite its contributing to posttranslational modification of virion proteins. Bo17 undergoes an alternative splicing that generates two different products of expression. In contrast to the full-length form of the protein, the shortened spliced form is devoid of enzymatic activity and confers to BoHV-4 the potential to fine-tune the core 2 branching activity of the infected cell, mechanisms to regulate the activity of glycosyltransferases from the Golgi apparatus, overview. O-Glycomic profile analysis of wild-type and mutant strains. Sole expression of either of the two Bo17-encoded proteins can influence BoHV-4 growth. Bo17 expression and splicing may affect the structure of O-glycans on BoHV-4 virions and in particular on glycoprotein gp180
physiological function
the mucin-type core 2 1,6-N-acetylglucosaminyltransferase enzyme (C2GnT-M), encoded by the GCNT3 gene, is a glycosyltransferase enzyme whose expression is altered in cancer processes. GCNT3 catalyzes the formation of core 2 O-glycan, core 4 O-glycan and I branches and its pattern of expression is mainly associated with colorectal cancer (CRC) prognosis. GCNT3 transfection in certain CRC cells reduces cell proliferation, adhesion, invasion, and induced cell death, and also inhibits tumor growth in vivo. Role of glycosyltransferase enzyme GCNT3 in colon and ovarian cancer prognosis and chemoresistance, overview. Integrated transcriptomic and proteomic analyses reveal that GCNT3 is linked to cellular cycle, mitosis and proliferation, response to drugs and metabolism pathways. GCNT3 overexpression contributes to reduce 5-fluorouracil resistance in metastatic CRC cells. GCNT3 also diminishes cell invasion and VEGFA expression in EOC cells. GCNT3 is a cancer prognostic factor. GCNT3 diminishes cell proliferation, invasion and alters metabolic properties of CRC cells. GCNT3 high-expressing Stage III-IV EOC patients have better response to conventional treatment and clinical outcome
physiological function
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the mucin-synthesizing core 2 beta-1,6 N-acetylglucosaminyltransferase (GCNT3/C2GNT) plays a significant role in mucin biosynthesis
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physiological function
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Bovine herpesvirus 4 modulates its beta-1,6-N-acetylglucosaminyltransferase activity through alternative splicing. The enzyme is a homologue of the cellular core 2 protein beta-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M), which is a key player for the synthesis of complex O-glycans
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additional information
Keratin 1 retains C2GnT-M in the Golgi by interacting with its cytoplasmic tail via the rod domain. Keratin 1 plays a critical role in the regulation of O-glycosylation pathways
additional information
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Keratin 1 retains C2GnT-M in the Golgi by interacting with its cytoplasmic tail via the rod domain. Keratin 1 plays a critical role in the regulation of O-glycosylation pathways
additional information
quantum mechanical/molecular modeling using enzyme crystal structures, PDB IDs 2GAK and 2GAM, as templates. C2GnT may occur in an open conformation, and a closed conformation. The location of the C2GnT-conserved Glu320 residue structurally corresponds to the catalytic base found in other glycosyltransferases with the GT-A fold. The enzyme-substrate system (C2GnT-UDP-GlcNAc-Galb1-3GalNAc ternary complex) consists of 379 amino acids, eight water molecules, donor, and acceptor, active site model
additional information
the two isoforms of Bo17 are expressed in BoHV-4 infected cells, but enzymatic assays revealed that the spliced form is not active
additional information
no effect of core fucosylation of substrate on the glycosyltransferase activity of GnT-III, overview
additional information
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the splicing of the Bo17 gene gives the potential to BoHV-4 to fine-tune the global level of core 2 branching activity in the infected cell. Analysis of the structures of O-glycans isolated from cells mock infected or infected with the Bo17 Del, Bo17 MuDir, Bo17 MuDir Rev, Bo17 Spliced, and Bo17 Spliced Rev strains of BoHV-4
additional information
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the two isoforms of Bo17 are expressed in BoHV-4 infected cells, but enzymatic assays revealed that the spliced form is not active
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