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

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-Nacetylglucosaminyltransferase 6 (core 3
synthase))
Neeru 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 (NMS, PR, ST, PWC)
Published in Atlas Database: May 2009
Online updated version: http://AtlasGeneticsOncology.org/Genes/B3GNT6ID44427ch11q13.html
DOI: 10.4267/2042/44726
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Description
Identity
Human B3GNT6 gene is 7,111 bp in length, composed
of 2 exons and 1 intron, and located at chromosome
11q13.4.
Other names: B3Gn-T6; beta3GNT6; BGnT-6; Beta1,3-N-acetylglucosaminyltransferase-6; Beta3Gn-T6;
C3S; Core 3 synthase; MGC119334; MGC119336;
MGC119337
HGNC (Hugo): B3GNT6
Location: 11q13.5
Local order: -NANote
B3GNT6 is a single-pass type II membrane protein
belonging to the glycosyltransferase 31 family.
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
DNA/RNA
Note
Human UDP-GlcNAc:GalNAca1-Ser/Thr beta-1,3-Nacetylglucosaminyltransferase 6 (core 3 synthase) has
384 amino acids and 43 KDa molecular weight.
Note
Human B3GNT6 is located on chromosome 11 in the
region of q13.4.
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.
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).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(4)
353
B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase))
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.
Expression
B3GNT6/C3S gene expression is restricted to mucussecretory 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 mucussecretory 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.
References
Brockhausen I. Biosynthesis and functions of O-glycans and
regulation of mucin antigen expression in cancer. Biochem Soc
Trans. 1997 Aug;25(3):871-4
Iwai T, Inaba N, Naundorf A, Zhang Y, Gotoh M, Iwasaki H,
Kudo T, Togayachi A, Ishizuka Y, Nakanishi H, Narimatsu H.
Molecular cloning and characterization of a novel UDPGlcNAc:GalNAc-peptide
beta1,3-Nacetylglucosaminyltransferase (beta 3Gn-T6), an enzyme
synthesizing the core 3 structure of O-glycans. J Biol Chem.
2002 Apr 12;277(15):12802-9
Implicated in
Gastric and Colorectal carcinomas
Iwai T, Kudo T, Kawamoto R, Kubota T, Togayachi A, Hiruma
T, Okada T, Kawamoto T, Morozumi K, Narimatsu H. Core 3
synthase is down-regulated in colon carcinoma and profoundly
suppresses the metastatic potential of carcinoma cells. Proc
Natl Acad Sci U S A. 2005 Mar 22;102(12):4572-7
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
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(4)
Sharma NM, et al.
354
B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase))
Brockhausen I. Mucin-type O-glycans in human colon and
breast cancer: glycodynamics and functions. EMBO Rep. 2006
Jun;7(6):599-604
This article should be referenced as such:
Sharma NM, Radhakrishnan P, Tan S, Cheng PW. B3GNT6
(UDP-GlcNAc:betaGal
beta-1,3-Nacetylglucosaminyltransferase 6 (core 3 synthase)). Atlas
Genet Cytogenet Oncol Haematol. 2010; 14(4):353-355.
An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun
J, Xia L. Increased susceptibility to colitis and colorectal tumors
in mice lacking core 3-derived O-glycans. J Exp Med. 2007 Jun
11;204(6):1417-29
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(4)
Sharma NM, et al.
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