Recombinant Mouse Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (Mgat3), partial

Function

It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked sugar chains, called bisecting N-acetylglucosamine (GlcNAc). It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides (PubMed:11986323, PubMed:25592972). The addition of this bisecting GlcNAc residue alters not only the composition, but also the conformation of the N-glycan. The introduction of the bisecting GlcNAc residue results in the suppression of further processing and elongation of N-glycans, precluding the formation of beta-1,6 GlcNAc branching, catalyzed by MGAT5 since it is unable to use the bisected oligosaccharide as a substrate (By similarity). Addition of bisecting N-acetylglucosamine to CDH1/E-cadherin modulates CDH1 cell membrane location. Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc- formation which modulates sialylation levels and plays a role in cell migration regulation (By similarity). In brain, addition of bisecting N-acetylglucosamine to BACE1 blocks its lysosomal targeting in response to oxidative stress and further degradation which increases its location to early endosome and the APP cleavage (PubMed:25592972, PubMed:26467158). Adds bisecting GlcNAc residue to complex-type N-linked-glycans attached on fragment crystallizable (Fc) of IgGs. Readily converts fucosylated and non-fucosylated core glycoforms with terminal GlcNAcs on both antennae. Prior galactosylation of GlcNAc on the alpha(1->3) Man branch prevents N-glycan bisection, whereas galactosylation of GlcNAc on the alpha(1->6) Man branch is permissive

Subcellular Location

Golgi apparatus, Golgi stack membrane (Single-pass type II membrane protein)

Tissue Specificity

Highly expressed in brain and kidney and to a much lesser extent in stomach, heart, intestine, uterus, testis, ovary and lung. Not present in spleen, liver and muscle. In brain, expressed in neurons of hippocampus (PubMed:11986323)

Subunit

Interacts with MGAT4D

Pathway

Protein modification; protein glycosylation

• Bhaumik M. et al. Cloning and chromosomal mapping of the mouse Mgat3 gene encoding N-acetylglucosaminyltransferase III. — Gene (1995)
• Priatel J.J. et al. Isolation, characterization and inactivation of the mouse Mgat3 gene: the bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproduction. — Glycobiology (1997)
• Bhattacharyya R. et al. Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII) induces neurological and other traits absent in mice that lack GlcNAc-TIII. — J. Biol. Chem. (2002)
• Iijima J. et al. Cell-cell interaction-dependent regulation of N-acetylglucosaminyltransferase III and the bisected N-glycans in GE11 epithelial cells. Involvement of E-cadherin-mediated cell adhesion. — J. Biol. Chem. (2006)
• Huang H.H. et al. A testis-specific regulator of complex and hybrid N-glycan synthesis. — J. Cell Biol. (2010)
• Kizuka Y. et al. An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease. — EMBO Mol. Med. (2015)
• Kizuka Y. et al. Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions. — Biochem. J. (2016)