B3GAT2

Official Full Name

beta-1,3-glucuronyltransferase 2

Organism

Homo sapiens

GeneID

135152

Background

The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. [provided by RefSeq, Jul 2008]

Synonyms

GLCATS;

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Detailed Information

Glucuronosyltransferase 2 is encoded by the B3GAT2 gene in humans. This transmembrane protein, belongs to the glucuronyltransferase family, which catalyzes the transfer of β-1, 3-linked glucuronic acid to glycoproteins containing galactose-β-1-4GlcNAc.

Methylated B3GAT2 is a Potential Biomarkers for Barrett’s Esophagus

Barrett's esophagus (BE) is a precancerous state in which normal esophageal squamous epithelium (SQ) is replaced by special intestinal metaplasia. It is the putative precursor of esophageal adenocarcinoma (EAC) and the strongest risk factor for this type of cancer. Unfortunately, many BE patients have not been diagnosed according to current BE screening guidelines. Abnormal DNA methylation is an epigenetic change that is common in many human cancers. Recent study have discovered two genes, B3GAT2 and ZNF793, which are aberrantly methylated in BE. Clinical validation studies confirmed that B3GAT2 methylation levels were significantly higher in BE samples than in control tissues. And aberrant DNA hypermethylation of the B3GAT2 promoter region has recently been reported in colon cancer, especially in the CpG island methylator phenotype (CIMP) subtype.

B3GAT2 Participate in the Biosynthesis of the HNK-1 Carbohydrate Epitope

Glycosylation is a major post-translational protein modification, especially for cell surface proteins, which play important roles in a variety of cellular functions, including recognition and adhesion.

B3GAT2 is mainly expressed in neuronal tissues and is involved in the initial steps of proteoglycan synthesis including the synthesis of HNK-1 carbohydrate epitope. It is speculated that HNK-1 carbohydrates are involved in cell-cell and cell-matrix interactions, such as neural crest cell migration, neuron-astrocyte adhesion, and preferential neurite outgrowth of motor neurons.

B3GAT2 Fig 1. Biosynthesis and structural features of the HNK-1 carbohydrate (Ippei et al. The Journal of Biochemistry, 2008).

B3GAT2 is highly expressed in certain areas of the mouse brain, such as the CA2/CA3 hippocampal subfield, the neocortical layers V and VI, and several nuclei of the thalamus. In mice lacking the B3GAT1 gene, the widely distributed HNK-1 brain expression is almost completely lost. As the same time, B3GAT2 intron SNPs are associated with SCZ as well as cortical surface area. The results of this study suggest that the effect on the biosynthesis of neuronal epitope HNK-1 may decrease the cortical surface area through common variation of B3GAT2, thereby increasing the risk of SCZ. Independent replication is needed to determine whether this is a true positive finding, and subsequent efforts can elucidate the functionality behind the relevant markers.

References:

Hinoue T, et al. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Research. 2012.
Ippei Morita, Yasuhiko Kizuka, Shinako Kakuda, Shogo Oka; Expression and Function of the HNK-1 Carbohydrate. The Journal of Biochemistry, 2008.
Anna K.Kählerab et al. Candidate gene analysis of the human natural killer-1 carbohydrate pathway and perineuronal nets in schizophrenia: B3GAT2 is associated with disease risk and cortical surface area. Biological Psychiatry. 2011.

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