GnTII

N-acetylglucosaminyltransferase II (GnT-II) is a Golgi-resident glycosyltransferase that initiates the second branch in the maturation of N-linked glycans. In humans the enzyme is encoded by the MGAT2 gene. It is a type II transmembrane protein with its catalytic domain oriented toward the Golgi lumen.

GnT-II functions in the processing of complex N-glycans by transferring N-acetylglucosamine (GlcNAc) in a β1-2 linkage to a core mannose residue of N-glycans, enabling the formation of biantennary (and further extended) complex N-glycans. This step follows GnT-I activity and is a prerequisite for subsequent branching by other glycosyltransferases, contributing to the diversity and maturation of glycoprotein glycans. Proper GnT-II activity supports correct protein folding, stability, and trafficking, and its function is coordinated with other glycosylation enzymes in the Golgi.

Genetic mutations or reduced expression of MGAT2 lead to congenital disorders of glycosylation type II (CDG-II), reflecting disrupted N-glycan branching. Affected individuals typically exhibit developmental and growth delays, hypotonia, liver involvement, and immune system abnormalities, with biochemical signatures showing altered complex glycan structures.

In research and biotechnology, GnT-II is studied to understand the role of glycan branching in cell signaling and adhesion, and to influence glycoprotein design in glycoengineering. Inhibitors or gene-silencing approaches targeting GnT-II are used to probe the impact of glycosylation on protein maturation and function.