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B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase))

Identity

Other namesB3Gn-T6
beta3GNT6
BGnT-6
Beta-1,3-N-acetylglucosaminyltransferase-6
Beta3Gn-T6
C3S
Core 3 synthase
MGC119334
MGC119336
MGC119337
HGNC (Hugo) B3GNT6
LocusID (NCBI) 192134
Location 11q13.5
Location_base_pair Starts at 76745385 and ends at 76753005 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order -NA-
Note B3GNT6 is a single-pass type II membrane protein belonging to the glycosyltransferase 31 family.

DNA/RNA

Note Human B3GNT6 is located on chromosome 11 in the region of q13.4.
 
  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).
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-

Protein

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.
 
  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.
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.

Implicated in

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.
  

External links

Nomenclature
HGNC (Hugo)B3GNT6   24141
Cards
AtlasB3GNT6ID44427ch11q13
Entrez_Gene (NCBI)B3GNT6  192134  UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase)
GeneCards (Weizmann)B3GNT6
Ensembl (Hinxton)ENSG00000198488 [Gene_View]  chr11:76745385-76753005 [Contig_View]  B3GNT6 [Vega]
ICGC DataPortalENSG00000198488
cBioPortalB3GNT6
AceView (NCBI)B3GNT6
Genatlas (Paris)B3GNT6
WikiGenes192134
SOURCE (Princeton)NM_138706
Genomic and cartography
GoldenPath (UCSC)B3GNT6  -  11q13.5   chr11:76745385-76753005 +  11q13.4   [Description]    (hg19-Feb_2009)
EnsemblB3GNT6 - 11q13.4 [CytoView]
Mapping of homologs : NCBIB3GNT6 [Mapview]
OMIM615315   
Gene and transcription
Genbank (Entrez)AB073740 AK127544 AK172863 AK292773 AK313682
RefSeq transcript (Entrez)NM_138706
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NT_167190 NW_001838028 NW_004929380
Consensus coding sequences : CCDS (NCBI)B3GNT6
Cluster EST : UnigeneHs.352622 [ NCBI ]
CGAP (NCI)Hs.352622
Alternative Splicing : Fast-db (Paris)GSHG0005129
Alternative Splicing GalleryENSG00000198488
Gene ExpressionB3GNT6 [ NCBI-GEO ]     B3GNT6 [ SEEK ]   B3GNT6 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6ZMB0 (Uniprot)
NextProtQ6ZMB0  [Medical]
With graphics : InterProQ6ZMB0
Splice isoforms : SwissVarQ6ZMB0 (Swissvar)
Catalytic activity : Enzyme2.4.1.- [ Enzyme-Expasy ]   2.4.1.-2.4.1.- [ IntEnz-EBI ]   2.4.1.- [ BRENDA ]   2.4.1.- [ KEGG ]   
Domains : Interpro (EBI)Glyco_trans_31 [organisation]  
Related proteins : CluSTrQ6ZMB0
Domain families : Pfam (Sanger)Galactosyl_T (PF01762)   
Domain families : Pfam (NCBI)pfam01762   
DMDM Disease mutations192134
Blocks (Seattle)Q6ZMB0
Human Protein AtlasENSG00000198488 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ6ZMB0
HPRD16534
IPIIPI00847164   IPI00977839   IPI00977159   
Protein Interaction databases
DIP (DOE-UCLA)Q6ZMB0
IntAct (EBI)Q6ZMB0
FunCoupENSG00000198488
BioGRIDB3GNT6
InParanoidQ6ZMB0
Interologous Interaction database Q6ZMB0
IntegromeDBB3GNT6
STRING (EMBL)B3GNT6
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  galactosyltransferase activity  glycoprotein biosynthetic process  membrane  integral component of membrane  O-glycan processing  O-glycan processing, core 3  post-translational protein modification  cellular protein metabolic process  beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity  
Ontology : EGO-EBIGolgi membrane  galactosyltransferase activity  glycoprotein biosynthetic process  membrane  integral component of membrane  O-glycan processing  O-glycan processing, core 3  post-translational protein modification  cellular protein metabolic process  beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity  
Pathways : KEGGMucin type O-Glycan biosynthesis   
Protein Interaction DatabaseB3GNT6
Wikipedia pathwaysB3GNT6
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)B3GNT6
snp3D : Map Gene to Disease192134
SNP (GeneSNP Utah)B3GNT6
SNP : HGBaseB3GNT6
Genetic variants : HAPMAPB3GNT6
Exome VariantB3GNT6
1000_GenomesB3GNT6 
ICGC programENSG00000198488 
Somatic Mutations in Cancer : COSMICB3GNT6 
CONAN: Copy Number AnalysisB3GNT6 
Mutations and Diseases : HGMDB3GNT6
Mutations and Diseases : intOGenB3GNT6
Genomic VariantsB3GNT6  B3GNT6 [DGVbeta]
dbVarB3GNT6
ClinVarB3GNT6
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM615315   
MedgenB3GNT6
GENETestsB3GNT6
Disease Genetic AssociationB3GNT6
Huge Navigator B3GNT6 [HugePedia]  B3GNT6 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneB3GNT6
Homology/Alignments : Family Browser (UCSC)B3GNT6
Phylogenetic Trees/Animal Genes : TreeFamB3GNT6
Chemical/Protein Interactions : CTD192134
Chemical/Pharm GKB GenePA164741288
Clinical trialB3GNT6
Cancer Resource (Charite)ENSG00000198488
Other databases
Probes
Litterature
PubMed6 Pubmed reference(s) in Entrez
CoreMineB3GNT6
iHOPB3GNT6
OncoSearchB3GNT6

Bibliography

Biosynthesis and functions of O-glycans and regulation of mucin antigen expression in cancer.
Brockhausen I.
Biochem Soc Trans. 1997 Aug;25(3):871-4. (REVIEW)
PMID 9388564
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written05-2009Neeru M Sharma, Prakash Radhakrishnan, Shuhua Tan, Pi-Wan Cheng
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, USA

Citation

This paper should be referenced as such :
Sharma, NM ; Radhakrishnan, P ; Tan, S ; Cheng, PW
B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(4):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/B3GNT6ID44427ch11q13.html

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indexed on : Mon Sep 22 18:20:55 CEST 2014

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