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

Human B3GNT6 gene is 7,111 bp in length, composed of 2 exons and 1 intron, and located at chromosome 11q13.4.

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 3UTR.

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Human UDP-GlcNAc:GalNAca1-Ser/Thr beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase) has 384 amino acids and 43 KDa molecular weight.

B3GNT6/C3S is single-pass type II membrane protein belonging to the glycosyltransferase 31 family.

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.

Golgi Membrane.

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.

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.