Note |
Human B3GNT6 is located on chromosome 11 in the region of q13.4. |
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| The schematic representation of human B3GNT6 gene and its transcript (ATG, translation start codon; TGA, translation stop codon; UTR, Untranslated region; ORF, Open reading frame). |
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Description | Human B3GNT6 gene is 7,111 bp in length, composed of 2 exons and 1 intron, and located at chromosome 11q13.4. |
Transcription | B3GNT6 transcript contains two exons. Exon 1 is 121 bp and exon 2 is 1,917 bp. The exon 2 contains 1,155 bp ORF and 762 bp 3'UTR. |
Pseudogene | -NA- |
Note | Human UDP-GlcNAc:GalNAca1-Ser/Thr beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase) has 384 amino acids and 43 KDa molecular weight. |
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| The predicted B3GNT6 structure contains a short N-terminal cytoplasmic tail (CT) (12 aa), a transmembrane domain (TM) (19 aa), a long stem region and catalytic domain (353 aa) at the C-terminal region. |
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Description | B3GNT6/C3S is single-pass type II membrane protein belonging to the glycosyltransferase 31 family. |
Expression | B3GNT6/C3S gene expression is restricted to mucus-secretory tissues. The level of beta3GnT6 transcript expressed in various human tissues as measured by the real time PCR revealed that the expression level was highest in the stomach, followed by the colon and small intestine. Skeletal muscle and testis expressed the beta3GnT6 transcript at a moderate level. The expression levels in the remaining tissues were very low or not detectable. Its expression was markedly down-regulated in gastric and colorectal carcinomas, which include both tumor tissues and cell lines-derived from these carcinomas. |
Localisation | Golgi Membrane. |
Function | B3GNT6/C3S enzyme catalyzes the transfer of GlcNAc from UDP-GlcNAc to GalNAcalpha1-Ser/Thr (Tn antigen) to form the core 3 structure (GlcNAcbeta1-3GalNAcalpha1-Ser/Thr). Core 3 can be extended by the addition of galactose and then other sugars to generate biologically important epitopes or serves as the precursor for the formation of core 4, which in turn can be further elaborated to form more complex structure. Core 3-containing O-glycans are found in the secreted mucins produced in the mucus-secretory tissues. Loss of core 3 synthase results in the loss of not only core 3 glycans but also core 4 glycans. Loss of core 3 could lead to the production of secreted mucins with compromised mucus protection function. As a result, mucus would be more dehydrated, bacteria would be inefficiently cleared from the system, and chronic inflammation would be developed, which eventually would result in development of cancer. A mouse model devoid of core 3 synthase gene has been shown to develop colon cancer. Because the loss of this gene leads to development of colon cancer, B3GNT6/C3S gene is a tumor suppressor gene. |
Homology | An alignment of the amino acid sequences of five B3GnTs made using ClustalW showed 41, 54, 42, and 35% sequence identity between B3GnT6 and B3GnT2, B3GnT3, B3GnT4, and B3GnT5, respectively, and this sequence similarity was limited to the putative catalytic domains. Five cysteine residues were conserved among these five B3GnTs. However, only B3GNT6/C3S exhibits significant core 3 synthase activity. |
Note | |
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Entity | Gastric and Colorectal carcinomas |
Note | Colorectal cancer, which is also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. Loss of function of the mucus layer is one major cause of this cancer. Globally, cancer of the colon and rectum is the third leading cause of cancer in males and the fourth leading cause of cancer in females. The frequency of colorectal cancer varies around the world. It is common in the Western world and is rare in Asia and Africa. In countries where the people have adopted western diets, the incidence of colorectal cancer is increasing. Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. Therefore, screening for the disease is recommended in individuals who are at increased risks. Prevention and early detection are key factors in controlling and curing colorectal cancer. Indeed, colorectal cancer is the second most preventable cancer, after lung cancer. |
Prognosis | B3GNT6/C3S is down-regulated in gastric and colorectal carcinomas, suggesting that it may be used as a marker for distinguishing between benign adenomas and premalignant lesions. |
Oncogenesis | O-linked oligosaccharides (O-glycans) are the primary components of the intestinal mucus layer that covers the gastrointestinal epithelium. This layer is a dense, carbohydrate-rich matrix that consists primarily of mucins containing multiple serine and threonine residues, which have been modified by O-glycans and account for 80-90% of the mucin mass. The mucus layer and epithelial cells comprise an intestinal barrier that protects epithelial and intestinal mucosal immune cells from potentially harmful luminal microflora and food components. Among all mucin glycan core structures, Core 3 and core 4 are unique to secreted mucins, which may play important roles in protecting the molecular integrity of these mucins and enable them to perform their functions under extreme harsh conditions, such as gastric and colonic environment. Loss of these functions resulted from the loss of core 3 synthase is thought to initiate oncogenesis in the gastrointestinal tract. |
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Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. |
An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun J, Xia L. |
J Exp Med. 2007 Jun 11;204(6):1417-29. Epub 2007 May 21. |
PMID 17517967 |
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Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. |
Brockhausen I. |
EMBO Rep. 2006 Jun;7(6):599-604. (REVIEW) |
PMID 16741504 |
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Molecular cloning and characterization of a novel UDP-GlcNAc:GalNAc-peptide beta1,3-N-acetylglucosaminyltransferase (beta 3Gn-T6), an enzyme synthesizing the core 3 structure of O-glycans. |
Iwai T, Inaba N, Naundorf A, Zhang Y, Gotoh M, Iwasaki H, Kudo T, Togayachi A, Ishizuka Y, Nakanishi H, Narimatsu H. |
J Biol Chem. 2002 Apr 12;277(15):12802-9. Epub 2002 Jan 30. |
PMID 11821425 |
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Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells. |
Iwai T, Kudo T, Kawamoto R, Kubota T, Togayachi A, Hiruma T, Okada T, Kawamoto T, Morozumi K, Narimatsu H. |
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4572-7. Epub 2005 Mar 8. |
PMID 15755813 |
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| Nomenclature |
HGNC (Hugo) | B3GNT6 24141 |
| Cards |
Atlas | B3GNT6ID44427ch11q13 |
Entrez_Gene (NCBI) | B3GNT6 "UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6" |
Aliases | "B3Gn-T6; BGnT-6; beta-1,3-Gn-T6; beta3Gn-T6" |
GeneCards (Weizmann) | B3GNT6 |
Ensembl hg19 (Hinxton) | ENSG00000198488 [Gene_View] |
Ensembl hg38 (Hinxton) | ENSG00000198488 [Gene_View]  ENSG00000198488 [Sequence] chr11:77034398-77041958 [Contig_View] B3GNT6 [Vega] |
ICGC DataPortal | ENSG00000198488 |
TCGA cBioPortal | B3GNT6 |
AceView (NCBI) | B3GNT6 |
Genatlas (Paris) | B3GNT6 |
SOURCE (Princeton) | B3GNT6 |
Genetics Home Reference (NIH) | B3GNT6 |
| Genomic and cartography |
GoldenPath hg38 (UCSC) | B3GNT6 - chr11:77034398-77041958 + 11q13.5 [Description] (hg38-Dec_2013) |
GoldenPath hg19 (UCSC) | B3GNT6 - 11q13.5 [Description] (hg19-Feb_2009) |
GoldenPath | B3GNT6 - 11q13.5 [CytoView hg19] B3GNT6 - 11q13.5 [CytoView hg38] |
ImmunoBase | ENSG00000198488 |
genome Data Viewer NCBI | B3GNT6 [Mapview hg19] |
OMIM | 615315 |
| Gene and transcription |
Genbank (Entrez) | AB073740 AK127544 AK172863 AK292773 AK313682 |
RefSeq transcript (Entrez) | NM_138706 |
RefSeq genomic (Entrez) | |
Consensus coding sequences : CCDS (NCBI) | B3GNT6 |
Alternative Splicing Gallery | ENSG00000198488 |
Gene Expression | B3GNT6 [ NCBI-GEO ] B3GNT6 [ EBI - ARRAY_EXPRESS ]
B3GNT6 [ SEEK ] B3GNT6 [ MEM ] |
Gene Expression Viewer (FireBrowse) | B3GNT6 [ Firebrowse - Broad ] |
Genevisible | Expression of B3GNT6 in : [tissues]  [cell-lines]  [cancer]  [perturbations]   |
BioGPS (Tissue expression) | 192134 |
GTEX Portal (Tissue expression) | B3GNT6 |
Human Protein Atlas | ENSG00000198488-B3GNT6 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
UniProt/SwissProt | Q6ZMB0 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
NextProt | Q6ZMB0 [Sequence] [Exons] [Medical] [Publications] |
With graphics : InterPro | Q6ZMB0 |
Splice isoforms : SwissVar | Q6ZMB0 |
PhosPhoSitePlus | Q6ZMB0 |
Domains : Interpro (EBI) | Glyco_trans_31 |
Domain families : Pfam (Sanger) | Galactosyl_T (PF01762) |
Domain families : Pfam (NCBI) | pfam01762 |
Conserved Domain (NCBI) | B3GNT6 |
Blocks (Seattle) | B3GNT6 |
Superfamily | Q6ZMB0 |
Human Protein Atlas [tissue] | ENSG00000198488-B3GNT6 [tissue] |
Peptide Atlas | Q6ZMB0 |
HPRD | 16534 |
IPI | IPI00847164 IPI00977839 IPI00977159 |
| Protein Interaction databases |
DIP (DOE-UCLA) | Q6ZMB0 |
IntAct (EBI) | Q6ZMB0 |
BioGRID | B3GNT6 |
STRING (EMBL) | B3GNT6 |
ZODIAC | B3GNT6 |
| Ontologies - Pathways |
QuickGO | Q6ZMB0 |
Ontology : AmiGO | "Golgi membrane Golgi apparatus protein glycosylation acetylglucosaminyltransferase activity acetylgalactosaminyltransferase activity galactosyltransferase activity N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity glycoprotein biosynthetic process membrane integral component of membrane O-glycan processing O-glycan processing, core 3 protein phosphopantetheinylation poly-N-acetyllactosamine biosynthetic process beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity acetylgalactosaminyl-O-glycosyl-threonyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity acetylgalactosaminyl-O-glycosyl-seryl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity" |
Ontology : EGO-EBI | "Golgi membrane Golgi apparatus protein glycosylation acetylglucosaminyltransferase activity acetylgalactosaminyltransferase activity galactosyltransferase activity N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity glycoprotein biosynthetic process membrane integral component of membrane O-glycan processing O-glycan processing, core 3 protein phosphopantetheinylation poly-N-acetyllactosamine biosynthetic process beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity acetylgalactosaminyl-O-glycosyl-threonyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity acetylgalactosaminyl-O-glycosyl-seryl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity" |
Pathways : KEGG | Mucin type O-Glycan biosynthesis |
REACTOME | Q6ZMB0 [protein] |
REACTOME Pathways | R-HSA-913709 [pathway] |
NDEx Network | B3GNT6 |
Atlas of Cancer Signalling Network | B3GNT6 |
Wikipedia pathways | B3GNT6 |
| Orthology - Evolution |
OrthoDB | 192134 |
GeneTree (enSembl) | ENSG00000198488 |
Phylogenetic Trees/Animal Genes : TreeFam | B3GNT6 |
HOGENOM | Q6ZMB0 |
Homologs : HomoloGene | B3GNT6 |
Homology/Alignments : Family Browser (UCSC) | B3GNT6 |
| Gene fusions - Rearrangements |
Fusion : Fusion_Hub | B3GNT6--GABPB2 B3GNT6--MPHOSPH8 B3GNT6--RP11-191A15.2 |
Fusion : Quiver | B3GNT6 |
| Polymorphisms : SNP and Copy number variants |
NCBI Variation Viewer | B3GNT6 [hg38] |
dbVar | B3GNT6 |
ClinVar | B3GNT6 |
Monarch | B3GNT6 |
1000_Genomes | B3GNT6 |
Exome Variant Server | B3GNT6 |
GNOMAD Browser | ENSG00000198488 |
Varsome Browser | B3GNT6 |
Genomic Variants (DGV) | B3GNT6 [DGVbeta] |
DECIPHER | B3GNT6 [patients] [syndromes] [variants] [genes] |
CONAN: Copy Number Analysis | B3GNT6 |
| Mutations |
ICGC Data Portal | B3GNT6 |
TCGA Data Portal | B3GNT6 |
Broad Tumor Portal | B3GNT6 |
OASIS Portal | B3GNT6 [ Somatic mutations - Copy number] |
Somatic Mutations in Cancer : COSMIC | B3GNT6 [overview] [genome browser] [tissue] [distribution] |
Somatic Mutations in Cancer : COSMIC3D | B3GNT6 |
Mutations and Diseases : HGMD | B3GNT6 |
LOVD (Leiden Open Variation Database) | Whole genome datasets |
LOVD (Leiden Open Variation Database) | LOVD - Leiden Open Variation Database |
LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
BioMuta | search B3GNT6 |
DgiDB (Drug Gene Interaction Database) | B3GNT6 |
DoCM (Curated mutations) | B3GNT6 (select the gene name) |
CIViC (Clinical Interpretations of Variants in Cancer) | B3GNT6 (select a term) |
intoGen | B3GNT6 |
NCG6 (London) | select B3GNT6 |
Cancer3D | B3GNT6(select the gene name) |
Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
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OMIM | 615315 |
Orphanet | |
DisGeNET | B3GNT6 |
Medgen | B3GNT6 |
Genetic Testing Registry | B3GNT6
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NextProt | Q6ZMB0 [Medical] |
GENETests | B3GNT6 |
Target Validation | B3GNT6 |
Huge Navigator |
B3GNT6 [HugePedia] |
ClinGen | B3GNT6 |
| Clinical trials, drugs, therapy |
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MyCancerGenome | B3GNT6 |
Protein Interactions : CTD | |
Pharm GKB Gene | PA164741288 |
Pharos | Q6ZMB0 |
Clinical trial | B3GNT6 |
| Miscellaneous |
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canSAR (ICR) | B3GNT6 (select the gene name) |
Harmonizome | B3GNT6 |
DataMed Index | B3GNT6 |
| Probes |
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| Litterature |
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PubMed | 10 Pubmed reference(s) in Entrez |
GeneRIFs | Gene References Into Functions (Entrez) |
EVEX | B3GNT6 |